Williams, Katherine L. Sukupolvi-Petty, Soila Beltramello, Martina Johnson, Syd Sallusto, Federica Lanzavecchia, Antonio Diamond, Michael S. Harris, Eva 2013-02-14 Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV). At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs) and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel in vitro suppression-of- enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease in vivo. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease. application/pdf https://n2t.net/ark:/12658/srd1319191 https://susi.usi.ch/global/documents/319191 https://susi.usi.ch/documents/319191/files/Williams_PP_2013.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1003157 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319191 info:eu-repo/semantics/openAccess CC BY Plos pathogens. - 2013, vol. 9, no. 2, p. e1003157 info:eu-repo/classification/udc/61 Therapeutic efficacy of antibodies lacking FcγR against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies http://purl.org/coar/resource_type/c_6501